Abstract：At present, due to wide indications, high safety and remarkable efficacy, peptide drugs have been widely used in the prevention, diagnosis and treatment of tumors, hepatitis, diabetes, AIDS and many other diseases. However, natural peptides are easy to be degraded when entering biological systems and can be quickly removed through the blood circulation. Thus, peptide-based nanomedicine systems, which are fabricated by physical encapsulation and chemical conjugation, have become a hotspot for researchers to construct the novel and intelligent drug delivery systems, because of high biological safety, good biocompatibility, and easy modification. Herein, we firstly described the common biological properties of bioactive peptides, such as antibacterial, antiviral, and antitumor effects, and then summarized the research on the construction of nanomedicine for drug delivery based on the bioactive peptides. Finally, we provided perspectives on the development of peptide-based nanomedicine which shows considerably promising future in the drug delivery.
郑珊珊, 蔡悦, 龚瑜贝, 洪煜璐, 孙漩嵘. 纳米载体用于包载生物活性多肽的研究进展[J]. 中国生物医学工程学报, 2023, 42(2): 242-251.
Zheng Shanshan, Cai Yue, Gong Yubei, Hong Yulu, Sun Xuanrong. Research Progress onTherapeutic Peptides Loaded with Nanocarriers. Chinese Journal of Biomedical Engineering, 2023, 42(2): 242-251.
[1] Sur S, Rathore A, Dave V, et al. Recent developments in functionalized polymer nanoparticles for efficient drug delivery system[J]. Nano-Structures & Nano-Objects, 2019, 20: 100397. [2] Shi Jinjun, Kantoff PW, Wooster R, et al. Cancer nanomedicine: progress, challenges and opportunities[J]. Nat Rev Cancer, 2017, 17(1): 20-37. [3] Prabhakar U, Maeda H, Jain RK, et al. Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology[J]. Cancer Research, 2013, 73(8): 2412-2417. [4] Sun Lova, Joh DY, Al-Zaki A, et al. Theranostic application of mixed gold and superparamagnetic iron oxide nanoparticle micelles in glioblastoma multiforme[J]. J Biomed Nanotechnol, 2016, 12(2): 347-356. [5] Feng Guangxue, Fang Yuan, Liu Jie, et al. Multifunctional conjugated polymer nanoparticles for image-guided photodynamic and photothermal therapy[J]. Small, 2017, 13(3): 1602807. [6] Guthi JS, Yang SG, Huang Gang, et al. MRI-visible micellar nanomedicine for targeted drug delivery to lung cancer cells[J]. Mol Pharm, 2010, 7(1): 32-40. [7] Sivaraj R, Rahman PKSM, Rajiv P, et al. Biogenic copper oxide nanoparticles synthesis using Tabernaemontana divaricate leaf extract and its antibacterial activity against urinary tract pathogen[J]. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2014, 133: 178-181. [8] Esmaeili A, Ghobadianpour S. Vancomycin loaded superparamagnetic MnFe2O4 nanoparticles coated with PEGylated chitosan to enhance antibacterial activity[J]. Int J Pharm, 2016, 501(1-2): 326-330. [9] Mirza Z, Karim S. Nanoparticles-based drug delivery and gene therapy for breast cancer: recent advancements and future challenges[J]. Seminars in Cancer Biology, 2021, 69: 226-237. [10] Adair JH, Parette MP, Altinoglu EI, et al. Nanoparticulate alternatives for drug delivery[J]. ACS Nano, 2010, 4(9): 4967-4970. [11] Chen Long, Patrone N, Liang Junfeng. Peptide self-assembly on cell membranes to induce cell lysis[J]. Biomacromolecules, 2012, 13(10): 3327-3333. [12] Li Yaohao, Clark KA, Tan Zhongping. Methods for engineering therapeutic peptides[J]. Chinese Chemical Letters, 2018, 29(7): 1074-1078. [13] Hamman JH, Enslin GM, Kotze AF. Oral delivery of peptide drugs: barriers and developments[J]. BioDrugs, 2005, 19(3): 165-177. [14] Qu Xiaoyan, Liu Zhengqing, Ma Bohan, et al. All in one theranostic nanoplatform enables efficient anti-tumor peptide delivery for triple-modal imaging guided cancer therapy[J]. Nano Research, 2019, 3(12): 593-599. [15] Pal I, Brahmkhatri VP, Bera S, et al. Enhanced stability and activity of an antimicrobial peptide in conjugation with silver nanoparticle[J]. Journal of Colloid and Interface Science,2016,483:385-393. [16] Blachman A, Funez F, Birocco AM, et al. Targeted anti-inflammatory peptide delivery in injured endothelial cells using dermatan sulfate/chitosan nanomaterials[J]. Carbohydrate Polymers, 2020, 230:115610. [17] Bozzuto G, Molinari A. Liposomes as nanomedical devices[J]. Int J Nanomedicine, 2015, 10: 975-999. [18] Hwang D, Ramsey JD, Kabanov AV. Polymeric micelles for the delivery of poorly soluble drugs: from nanoformulation to clinical approval[J]. Adv Drug Deliv Rev, 2020, 156: 80-118. [19] Wang Jianqiu, Sui Meihua, Fan Weimin. Nanoparticles for tumor targeted therapies and their pharmacokinetics[J]. Curr Drug Metab, 2010, 11(2): 129-141. [20] Mu Jingqing, Zhong Haiping, Zou Hui, et al. Acid-sensitive PEGylated paclitaxel prodrug nanoparticles for cancer therapy: effect of PEG length on antitumor efficacy[J]. J Control Release, 2020, 326: 265-275. [21] Li Jing, Yin Tingjie, Wang Lei, et al. Biological evaluation of redox-sensitive micelles based on hyaluronic acid-deoxycholic acid conjugates for tumor-specific delivery of paclitaxel[J]. Int J Pharm, 2015, 483(1-2): 38-48. [22] Zhou Huicong, Sun Huanjiao, Lv Shixian, et al. Legumain-cleavable 4-arm poly(ethylene glycol)-doxorubicin conjugate for tumor specific delivery and release[J]. Acta Biomater, 2017, 54: 227-238. [23] Fang J, Nakamura H, Maeda H. The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect[J]. Adv Drug Deliv Rev, 2011, 63(3): 136-151. [24] Glasgow MD, Chougule MB. Recent developments in active tumor targeted multifunctional nanoparticles for combination chemotherapy in cancer treatment and imaging[J]. J Biomed Nanotechnol, 2015, 11(11): 1859-1898. [25] Spirescu VA, Chircov C, Grumezescu AM, et al. Inorganic nanoparticles and composite films for antimicrobial therapies[J]. Int J Mol Sci, 2021, 22(9): 4595. [26] Yang Qian, Peng Jinrong, Shi Kun, et al. Rationally designed peptide-conjugated gold/platinum nanosystem with active tumor-targeting for enhancing tumor photothermal-immunotherapy[J]. Journal of Controlled Release, 2019, 308: 29-43. [27] Niu Zhigao, Samaridou E, Jaumain E, et al. PEG-PGA enveloped octaarginine-peptide nanocomplexes: an oral peptide delivery strategy[J]. Journal of Controlled Release, 2018, 276(28): 125-139. [28] Allen TM, Cullis PR. Drug delivery systems: entering the mainstream[J]. Science, 2004, 303(5665): 1818-1822. [29] Vlieghe P, Lisowski V, Martinez J, et al. Synthetic therapeutic peptides: science and market[J]. Drug Discovery Today, 2010, 15(1-2): 40-56. [30] Shartouny JR, Jacob J. Mining the tree of life: host defense peptides as antiviral therapeutics[J]. Seminars in Cell and Developmental Biology, 2019, 88: 147-155. [31] Grgü A, Genda E, Ylmaz FM. Bioactive peptides derived from plant origin by-products: Biological activities and techno-functional utilizations in food developments-a review[J]. Food Research International, 2020, 136: 109504. [32] Zamora-Sillero J, Gharsallaoui A, Prentice C. Peptides from fish by-product protein hydrolysates and its functional properties: an overview[J]. Marine Biotechnology, 2018, 20: 118-130. [33] Lu Wuguang, Cai Xueting, Gu Zhenghua, et al. Production and characterization of hirudin variant-1 by SUMO fusion technology in E. coli[J]. Molecular Biotechnology, 2013, 53(1): 41-48. [34] Zhu Ningyi, Zhong Chao, Liu Tianqi, et al. Newly designed antimicrobial peptides with potent bioactivity and enhanced cell selectivity prevent and reverse rifampin resistance in gram-negative bacteria[J]. European Journal of Pharmaceutical Sciences, 2021, 158: 105665. [35] Lee TH, Hall KN, Aguilar MI. Antimicrobial peptide structure and mechanism of action: a focus on the role of membrane structure[J]. Curr Top Med Chem, 2016, 16(1): 25-39. [36] Karmakar S, Maity P, Halder A. Antimicrobial peptide NK-2 as an emerging therapeutic agent: a study with phospholipid membranes[J]. Materials Today: Proceedings, 2019, 18: 879-886. [37] Jodoin J, Hincke MT. Histone H5 is a potent antimicrobial agent and a template for novel antimicrobial peptides[J]. Scientific Reports, 2018, 8(1): 2411-2415. [38] Mookherjee N, Anderson MA, Haagsman HP, et al. Antimicrobial host defence peptides: functions and clinical potential[J]. Nature Reviews. Drug Discovery, 2020, 19(5): 311-332. [39] O′Neil DA. Innovation in infectious disease therapies from immunology[J]. Drug Discovery Today, 2021, 26(9): 2090-2094. [40] Ron-Doitch S, Sawodny B, Kuehbacher A, et al. Reduced cytotoxicity and enhanced bioactivity of cationic antimicrobial peptides liposomes in cell cultures and 3D epidermis model against HSV[J]. Journal of Controlled Release, 2016, 229: 163-171. [41] Magana M, Pushpanathan M, Santos AL, et al. The value of antimicrobial peptides in the age of resistance[J]. The Lancet Infectious Diseases, 2020, 20(9): e216-e230. [42] Kudrimoti M, Curtis A, Azawi S, et al. Dusquetide: a novel innate defense regulator demonstrating a significant and consistent reduction in the duration of oral mucositis in preclinical data and a randomized, placebo-controlled phase 2a clinical study[J]. Journal of Biotechnology, 2016, 239: 115-125. [43] Faya M, Kalhapure RS, Kumalo HM, et al. Conjugates and nano-delivery of antimicrobial peptides for enhancing therapeutic activity[J]. Journal of Drug Delivery Science and Technology, 2018, 44: 153-171. [44] Yazici H, Habib G, Boone K, et al. Self-assembling antimicrobial peptides on nanotubular titanium surfaces coated with calcium phosphate for local therapy[J]. Materials Science and Engineering: C, 2019, 94: 333-343. [45] Ron-Doitch S, Sawodny B, Kühbacher A, et al. Reduced cytotoxicity and enhanced bioactivity of cationic antimicrobial peptides liposomes in cell cultures and 3D epidermis model against HSV[J]. Journal of Controlled Release, 2016, 229: 163-171. [46] Casciaro B, Moros M, Rivera-Fernández S, et al. Gold-nanoparticles coated with the antimicrobial peptide esculentin-1a(1-21)NH2 as a reliable strategy for antipseudomonal drugs[J]. Acta Biomaterialia, 2017, 47: 170-181. [47] Serna N, Sanchez-Garcia L, Sanchez-Chardi A, et al. Protein-only, antimicrobial peptide-containing recombinant nanoparticles with inherent built-in antibacterial activity[J]. Acta Biomaterialia,2017, 60: 256-263. [48] Vuyyuri SB, Shidal C, Davis KR. Development of the plant-derived peptide lunasin as an anticancer agent[J]. Curr Opin Pharmacol, 2018, 41: 27-33. [49] Freiburghaus C, Janicke B, Lindmark-Mansson H, et al. Lactoferricin treatment decreases the rate of cell proliferation of a human colon cancer cell line[J]. J Dairy Sci, 2009, 92(6): 2477-2484. [50] Frokjaer S, Otzen DE. Protein drug stability: a formulation challenge[J]. Nat Rev Drug Discov, 2005, 4(4): 298-306. [51] Tarokh Z, Naderi-Manesh H, Nazari M. Towards prostate cancer gene therapy: development of a chlorotoxin-targeted nanovector for toxic (melittin) gene delivery[J]. Eur J Pharm Sci, 2017, 99: 209-218. [52] Zhang Lu, Jing Di, Jiang Nian, et al. Transformable peptide nanoparticles arrest HER2 signalling and cause cancer cell death in vivo[J]. Nature Nanotechnology, 2020, 15(2): 145-153. [53] Chen Long, Tu Zhigang, Voloshchuk N, et al. Lytic peptides with improved stability and selectivity designed for cancer treatment[J]. J Pharm Sci, 2012, 101(4): 1508-1517. [54] Chen Long, Patrone N, Liang Junfeng. Peptide self-assembly on cell membranes to induce cell lysis[J]. Biomacromolecules, 2012, 13(10): 3327-3333. [55] Sun Fude, Chen Long, Ding Xiufang, et al. High-resolution insights into the stepwise self-assembly of nanofiber from bioactive peptides[J]. Journal of Physical Chemistry B, 2017, 121(31): 7421-7430. [56] Wu Yuehuang, Ge Pengjin, Xu Weixia, et al. Cancer-targeted and intracellular delivery of Bcl-2-converting peptide with functional macroporous silica nanoparticles for biosafe treatment[J]. Materials Science & Enginearing C-Materials for Biological Applications, 2020, 108:110386. [57] Kouguchi T, Ito A, Iwai K, et al. Chicken collagen hydrolysate-derived peptides inhibit tumor necrosis factor-α-in-duced inflammatory response in endothelial cells[J]. Food Science and Technology Research, 2012, 5(18): 667-671. [58] Yu Wenlin, Field CJ, Wu Jianping. Purification and identification of anti-inflammatory peptides from spent hen muscle proteins hydrolysate[J]. Food Chem, 2018, 253: 101-107. [59] Peng Lin, Kong Xiaoyong, Wang Zongmin, et al. Baijiu vinasse as a new source of bioactive peptides with antioxidant and anti-inflammatory activity[J]. Food Chemistry, 2021, 339: 128159. [60] Mcmasters J, Panitch A. Collagen-binding nanoparticles for extracellular anti-inflammatory peptide delivery decrease platelet activation, promote endothelial migration, and suppress inflammation[J]. Acta Biomaterialia, 2017, 49:78-88. [61] Lin JB, Poh S, Panitch A. Controlled release of anti-inflammatory peptides from reducible thermosensitive nanoparticles suppresses cartilage inflammation[J]. Nanomedicine-Nanotechnology Biology and Medicine, 2016, 12(7): 2095-2100. [62] Kim M, Sahu A, Hwang Y, et al. Targeted delivery of anti-inflammatory cytokine by nanocarrier reduces atherosclerosis in Apo E-/-mice[J]. Biomaterials, 2020, 226: 119550. [63] Wei Jianchao, Hameed M, Wang Xin, et al. Antiviral activity of phage display-selected peptides against Japanese encephalitis virus infection in vitro and in vivo[J]. Antiviral Research, 2020, 174: 104673. [64] Ahmed A, Siman-Tov G, Keck F, et al. Human cathelicidin peptide LL-37 as a therapeutic antiviral targeting Venezuelan equine encephalitis virus infections[J]. Antiviral Res, 2019, 164:61-69. [65] Tripathi S, Wang Guangshun, White M, et al. Antiviral activity of the human cathelicidin, LL-37, and derived peptides on seasonal and pandemic influenza a viruses[J]. PLoS ONE, 2015, 10(4): e124706. [66] Currie SM, Gwyer FE, Mcfarlane AJ, et al. Cathelicidins have direct antiviral activity against respiratory syncytial virus in vitro and protective function in vivo in mice and humans[J]. J Immunol, 2016, 196(6): 2699-2710. [67] Bergman P, Walter-Jallow L, Broliden K, et al. The antimicrobial peptide LL-37 inhibits HIV-1 replication[J]. Curr HIV Res, 2007, 5(4): 410-415. [68] León R, Ruiz M, Valero Y, et al. Exploring small cationic peptides of different origin as potential antimicrobial agents in aquaculture[J]. Fish & Shellfish Immunology, 2020, 98: 720-727. [69] Agrawal A, Rangarajan N, Weisshaar JC. Resistance of early stationary phase E. coli to membrane permeabilization by the antimicrobial peptide Cecropin A[J]. Biochimica et Biophysica Acta (BBA)-Biomembranes, 2019, 1861(10): 182990. [70] Huang H, Pan C, Chen J. Grouper (epinephelus coioides) antimicrobial peptide epinecidin-1 exhibits antiviral activity against foot-and-mouth disease virus in vitro[J]. Peptides, 2018, 106: 91-95. [71] Hong Wei, Li Tian, Song Yu, et al. Inhibitory activity and mechanism of two scorpion venom peptides against herpes simplex virus type 1[J]. Antiviral Research, 2014, 102: 1-10. [72] Krajewski K, Marchand C, Long Yaqiu, et al. Synthesis and HIV-1 integrase inhibitory activity of dimeric and tetrameric analogs of indolicidin[J]. Bioorganic & Medicinal Chemistry Letters, 2004, 14(22): 5595-5598. [73] Monteiro JMC, Oliveira MD, Dias RS, et al. The antimicrobial peptide HS-1 inhibits dengue virus infection[J]. Virology, 2018, 514: 79-87. [74] Danielsen EM, Hansen GH. Impact of cell-penetrating peptides (CPPs) melittin and Hiv-1 Tat on the enterocyte brush border using a mucosal explant system[J]. Biochimica et Biophysica Acta (BBA) -Biomembranes, 2018, 1860(8): 1589-1599. [75] Harbig A, Mernberger M, Bittel L, et al. Transcriptome profiling and protease inhibition experiments identify proteases that activate H3N2 influenza A and influenza B viruses in murine airways[J]. Journal of Biological Chemistry, 2020, 295(33): 11388-11407. [76] Shartouny JR, Jacob J. Mining the tree of life: Host defense peptides as antiviral therapeutics[J]. Seminars in Cell & Developmental Biology, 2019, 88: 147-155. [77] Holthausen DJ, Lee SH, Kumar VT, et al. An amphibian host defense peptide is virucidal for human H1 hemagglutinin-bearing influenza viruses[J]. Immunity, 2017, 46(4): 587-595. [78] Rehm BHA. Bioengineering towards self-assembly of particulate vaccines[J]. Current Opinion in Biotechnology, 2017, 48: 42-53. [79] López-Sagaseta J, Malito E, Rappuoli R, et al. Self-assembling protein nanoparticles in the design of vaccines[J]. Computational and Structural Biotechnology Journal, 2016, 14: 58-68. [80] Finco O, Rappuoli R. Designing vaccines for the twenty-first century society[J]. Frontiers in Immunology, 2014, 5: 12. [81] Zeigler DF, Gage E, Roque R, et al. Epitope targeting with self-assembled peptide vaccines[J]. NPJ Vaccines, 2019, 4(1): 30-38. [82] Wang Zejun, Liu Wenhan, Shi Jiye, et al. Nanoscale delivery systems for cancer immunotherapy[J]. Materials Horizons, 2018, 5(3): 344-362. [83] Singh G, Zholobko O, Pillatzki A, et al. An amphiphilic invertible polymer as a delivery vehicle for a M2e-HA2-HA1 peptide vaccine against an influenza a virus in pigs[J]. Vaccine, 2019, 37(31): 4291-4301. [84] Bae J, Parayath N, Ma Wenxue, et al. BCMA peptide-engineered nanoparticles enhance induction and function of antigen-specific CD8(+) cytotoxic T lymphocytes against multiple myeloma: clinical applications[J]. Leukemia, 2020, 34(1): 210-223. [85] Zeng Liming, Liao Zonglang, Li Wenwei, et al. Non-covalent glycosylated gold nanoparticles/peptides nanovaccine as potential cancer vaccines[J]. Chinese Chemical Letters, 2020, 31(5): 1162-1164. [86] Zamani P, Navashenaq JG, Nikpoor AR, et al. MPL nano-liposomal vaccine containing P5 HER2/neu-derived peptide pulsed PADRE as an effective vaccine in a mice TUBO model of breast cancer[J]. Journal of Controlled Release, 2019, 303: 223-236. [87] Zamani P, Teymouri M, Nikpoor AR, et al. Nanoliposomal vaccine containing long multi-epitope peptide E75-AE36 pulsed PADRE-induced effective immune response in mice TUBO model of breast cancer[J]. European Journal of Cancer, 2020, 129: 80-96.
